NIAMS ARRA Chronicles

Researchers at the Henry Ford Health System based in Detroit, Mich., are searching for biomarkers for the kind of osteoarthritis (OA) that develops from a joint injury (post-traumatic osteoarthritis, or PTOA). Project leader Gary Gibson, Ph.D., and his colleagues are looking to find and validate microRNAs (miRNAs)—small noncoding nucleic acids—as biomarkers whose presence could yield information critical to clinical guidelines and treatment strategies for PTOA. The team—supported financially by the American Recovery and Reinvestment Act (ARRA) through the National Institute of Arthritis and Musculoskeletal and Skin Diseases—is investigating a family of newly discovered miRNAs in blood serum. Serum microRNAs have been shown to serve as biomarkers for other diseases such as cancer and heart disease.

Dr. Gibsonís group has already shown miRNA expression in cartilage cells, and has identified miRNAs in both human and mouse serum. Furthermore, he says, "We have shown that specific miRNAs have a markedly increased expression in cartilage as it degrades, suggesting a role in OA development." The scientists are now characterizing potential miRNA biomarkers in serum and joint tissue from an OA mouse model, and in serum from OA patients who have had an anterior cruciate ligament (ACL) injury. Biomarker validation studies will follow in a larger group of OA/ACL patients and in a PTOA sheep model.

Traditionally, the search for disease biomarkers has centered on larger molecules, such as proteins. According to Dr. Gibson, miRNAs have a number of advantages over larger biomarker candidates. Their smaller size and their chemical properties, for example, make them easier to detect and quantify. And, because there are fewer known miRNAs than proteins or carbohydrates, characterizing them is much easier.

Identifying biomarkers for disease has been a high priority for biomedical research for a number of years, and the researchers are excited about being part of the effort to develop more tools to help the millions of people with PTOA. Major support from ARRA has allowed Dr. Gibson to retain the services of his two research associates and to employ local university summer students for the project. ARRA funding has also enabled an essential collaboration with Mark Hurtig, D.V.M., Paul Marks, M.D., and Lawrence White, M.D., of the University of Torontoís ProKnee.ca consortium. They are contributing detailed clinical analyses and serum samples from OA patients who have had an ACL injury.

"We are excited about the promise of this project," says Dr. Gibson. "The development of biomarkers for the progression of PTOA will have benefits for predicting progression of OA pathology, provide an indication of pathways of disease pathology, and serve as a guide to therapeutic intervention in PTOA, as well as OA generally."

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The activity above was funded through the American Recovery and Reinvestment Act (ARRA). To track the progress of HHS activities funded through the ARRA, visit www.hhs.gov/recovery. To track all federal funds provided through the ARRA, visit www.recovery.gov.